| Objective Using Gegen Qilian Decoction with functions of “clearing the dampness of bowels” to intervene in ZDF rats with spontaneous diabetes mellitus type 2,through the detection of FBG,FINS,FFA,HbA1 c and other relevant indicators,then confirm the therapeutic actions of Gegen Qilian Decoction on spontaneous diabetes type 2.And also goes deep to the molecular level to observe the changes of key signal factors of IRS-2/PI3K/Akt signaling pathway in pancreatic tissue of ZDF rats before and after dosing,to further explore the mechanism actions of Gegen Qilian Decoction on protecting of islet cells.Methods Twenty-four male ZDF(fa/fa)rats were given Purina#5008 high fat diet,to induce type 2 diabetes mellitus,after successful modeling,they were randomly divided into Gegen Qinlian Decoction group,metformin group and model group,each group was 8 rats.eight male ZDF(fa/+)rats were set as a blank group.The rats in the model group and the blank group were given gavage with saline 10 m L/kg,Gegen Qinlian Decoction group was administered with Gegen Qinlian Decoction 13.8g/kg,and the metformin hydrochloride group was given gavage of metformin hydrochloride 0.16g/kg.After 8 weeks of administration,after fasting 12 h,second morning,blood samples were taken from the abdominal aorta and the pancreas was taken.blood samples detected FINS,HbA1 c and other indicators.the protein expression of IRS-2,p-IRS2,PI3 K p85,p-PI3 K p85,Akt2,p-Akt2 in pancreatic tissues was detected by Western blotting and immunohistochemistry(SP).The mRNA expression of IRS-2,PI3 K p85 and Akt2 in pancreas was detected by real-time qPCR(RT-qPCR).the pathological changes of pancreas were observed under microscope.Results 1.Blood biochemical test results:Compared with the blank group,FBG?FINS?FFA and HbA1 c in model group were significantly increased(P<0.01);Compared with the model group,FBG?FINS?FFA and HbA1 c in metformin group were decreased(P<0.05,P<0.01),the FBG?FINS?FFA and HbA1 c in the Gegen Qinlian decoction group were decreased(P<0.05,P<0.01).2.Pancreatic histopathology:There were a large number of normal islets in the pancreas of the blank group,the pancrestic tissue had clear organizational structure,and cells arranged in neat rows,acinar lobule was complete;only a small amount of residual fibrotic islets appeared in the pancreas of the model group rats,the pancrestic islets had disordant structure,the outline of acinar lobule has damaged,the inflammatory cells infiltrated significantly;The metformin group had scattered islets in the pancreas of rats,aciniular leaflet structure was more complete,showing a small amount of inflammatory cell infiltrated;Gegen Qinlian decoction group rat pancreas scattered in the distribution of new islets,compared with the model group,the numbers of Islets increased significantly,occasionally a small amount of inflammatory cell infiltrated.3.WB test results:Compared with the blank group,the expression of IRS-2,p-IRS2,PI3 K p85,Akt2 and p-Akt2 in the pancreas of the model group was significantly decreased(P<0.01);Compared with the model group,the expression of IRS-2,p-IRS2,PI3 K p85,p-Akt2 in the pancreas of metformin group was significantly increased(P <0.01),The expression of IRS-2,p-IRS2,PI3 K p85,p-PI3 K p85,Akt2 and p-Akt2 in the Gegen Qinlian decoction group were significantly increased(P<0.05,P<0.01).4.SP test results:Compared with the blank group,the protein expression of IRS-2,p-IRS2,PI3 K p85,p-PI3 K p85,Akt2 and p-Akt2 in the pancreas of the model group was significantly decreased(P<0.01);Compared with the model group,The protein expression of IRS-2?Akt2?PI3K p85?p-PI3 K p85?p-Akt2 in the pancreas of metformin group was significantly higher than that in the model group(P<0.05 or P<0.01);The protein expression of IRS-2?p-IRS2?PI3K p85?p-PI3 K p85?Akt2p-Akt2 in the Gegen Qinlian decoction group was significantly increased(P<0.01).5.RT-qPCR test results:Compared with the normal group,the mRNA expression of IRS-2,PI3 K p85 and Akt2 in model group was decreased(P<0.05,P<0.01);Compared with the model group,the mRNA expression of IRS-2,PI3 K p85,Akt2 in Gegen Qinlian decoction group and the mRNA expression of PI3 K p85 in metformin groups were increased(P<0.05,P<0.01).Conclusion 1.The obstruct of signaling pathway in IRS-2/PI3K/Akt of insulin led to injury of pancrestic islet cell and "Intestinal dampness" pathogenesis in early onset of type 2 diabetes,were related.2.“Clearing the dampness of bowels”and its representative square – Gegen Qinlian Decoction may achieve the goal of protecting pancreatic island cells and preventing type 2 diabetes by increasing the activity of signal transduction pathway in IRS-2/PI3K/Akt of the insulin. |
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